Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• ; ALFRED PASIEKA/SCIENCE PHOTO LIBRARY, No. 585105259. This content is not subject to CC BY 4.0. a. Photoredox catalytic cycles; b. absorption spectrum of photosensitizers. Therapeutic window indicates the most appropriate wavelength range to apply irradiation for biological applications. Graph

• /illustration/monoclonal-antibody-igg2a-lizenfreie-illustration/585105259?searchscope=image%2Cfilm&adppopup=true; ALFRED PASIEKA/SCIENCE PHOTO LIBRARY, No. 585105259. This content is not subject to CC BY 4.0. Schematic procedure of the divergent method developed by Sato et al. on histidine/tyrosine photoinduced

• modification. The antibody shown in this figure is from https://www.gettyimages.de/detail/illustration/monoclonal-antibody-igg2a-lizenfreie-illustration/585105259?searchscope=image%2Cfilm&adppopup=true; ALFRED PASIEKA/SCIENCE PHOTO LIBRARY, No. 585105259. This content is not subject to CC BY 4.0. Schematic

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• , they synthesized a large library of compounds of general structure 20. Furthermore, they extended the reaction to heteroaryl ketones to obtain a heterocycle containing β-amino ketones 21a–f [50]. The reaction tolerates a wide range of functional groups at the substrates, giving a wide structural scope

• , a library of acylamino acetamide derivatives 38 was synthesized from aliphatic and aromatic isocyanides and carboxylic acids, with good yields. When ammonia is replaced by methylamine, the main product incorporates methylamine as the amine component. This result indicates that HMTA is the main

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• polyethylene glycol (PEG) linker of various lengths is typically used to build a small library to identify a lead compound. For example, iVeliparib-AP6 (Figure 1) developed through this practice is a PROTAC that degrades poly(ADP-ribose) polymerase 2 (PARP2) selectively [5]. Results and Discussion The

• iVeliparib-AP6. As a common practice for small-molecule library synthesis, the identity and the purity of the reaction products of this simple, 3-step process were analyzed by LC–MS. Whereas the HPLC traces of the reaction mixtures showed one major product peak, the final product carried a barely noticeable

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• Gewald three-component reactions. Our focus was to create a representative, diverse and structurally complex library of building blocks, covering a range of shapes and chemical spaces, to facilitate formamide-based heteroannulation for the synthesis of the desired adducts. Thus, we employed aliphatic and

• anthranilic acid and B) access to heteroannulated pyrimidones by MCRs of suitably substituted heterocycles and formamide as C1 source. Access to the key building blocks 2–4 by employing three different nonisocyanide-based MCRs. Diversity and complexity were the essential features of our library of starting

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• repository to be employed freely for research purposes. In addition to HappyTools, there are other available open-source Python packages to analyze chromatographic and spectroscopic data. A cross-platform Python package named Aston can be used to process both UV–vis and MS data. The open-source library is

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• from either Sigma or Aaron Chemicals. Sponge material The sponge sample was obtained from the NatureBank [23] biota library housed at the Institute for Biomedicine and Glycomics, Griffith University, Australia. A voucher specimen of Suberea ianthelliformis (NB6014998; phylum Porifera, class

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• compounds with high yields (84–92%). The three most promising compounds of the library (13a, 13b, and 13c) were selected for further detailed characterization. In vitro evaluation was performed employing a high-performance liquid chromatography (HPLC)-based methodology, using the fluorogenic histone

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• this context, a unique example of the thiocyanation of a hydrazone was depicted [71]. A key feature of the approach is to circumvent the need for external oxidants. In the same vein, the group of Hajra [72] and Yang [73], independently, investigated the electrochemical C–H sulfonylation of a library of

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• porphyrin architectures, which could be used in supramolecular assemblies, catalysis, or sensing. In this work a library of arm-extended dodecasubstituted porphyrins was synthesized through the optimization of the classic Suzuki–Miyaura coupling of peripheral haloaryl substituents with a range of boronic

• of equivalents of boronic acid (Table 1, entries 10 and 11). Coupling at the meso-meta-phenyl position Optimization of conditions for OET-meta-BrPPs 12 (Scheme 3) were investigated next. Table 2 summarizes the reaction conditions used to synthesize a library of OET-meta-arylPPs as shown in Scheme 3

• observed with the β-ethyl CH3 resonances splitting into two separate chemical environments; however, the identity of the product synthesized was not fully characterized. In future, if reactivity for OET-o-BrPPs were to be further explored a larger library of ligands whether biphenyl-based or other could be

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• intramolecular aminocarbonylation using Mo(CO)6. Both catalytic approaches successfully produced the desired DBDAPs. As previously mentioned, organic synthesis is a crucial tool for preparing complex molecules of high value to industry. Frackenpohl et al. [13] designed and synthesized a new library of 2,3

Photoluminescence color-tuning with polymer-dispersed fluorescent films containing two fluorinated diphenylacetylene-type fluorophores

• Kazuki Kobayashi,
• Shigeyuki Yamada,
• Motohiro Yasui and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2682–2690, doi:10.3762/bjoc.20.225

• from our fluorinated diphenylacetylene library that exhibit different PL characteristics from blue to red in the solid state, as shown in Figure 2, and investigated their PL behavior and PL color-tuning potential. Results and Discussion Photoluminescence behavior of poly(methyl methacrylate) (PMMA

• ) states caused by the large ICT characteristics. Photoluminescence behavior of PMMA dispersion fluorescent films containing two fluorinated diphenylacetylenes Based on the solid-state fluorescent molecule library 1a–g developed by our group [20][21][22][23], we expected that white photoluminescent devices

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• this paper, we report a short and efficient synthesis of novel N-arylbenzo[h]quinazoline-2-amines. We have prepared a focused library of nineteen representative examples which have been submitted to cytotoxicity assays against a representative panel of eight cancer cell lines and several molecules gave

• describe a short and efficient synthesis for this type of novel skeleton and to prepare a focused library for these targets C. Further, we will report results on their cytotoxic activities. Results and Discussion Chemical synthesis For the preparation of our targets, we selected a flexible strategy which

• recently [18], gave the first target 4a (R = H) in 69% yield. In a similar way, we prepared a designed library with eighteen additional members 4b to 4s (Figure 2) having in the different ortho, meta and para positions either methyl groups, halogens (F, Cl) or methoxy groups. We have also prepared

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• found to be suitable for the preparation of a library of new biheterocyclic molecules bearing aromatic and aliphatic substituents as well as incorporating amino acid residues. The obtained furoxanotriazinones have demonstrated a moderate NO-releasing ability across a wide range of concentrations under

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• acid, base, or redox-labile parts of the linker [52]. Most recently, Wozniak et al. mapped the binding sites of a large small molecules library, which were equipped with a photo-crosslinker [110]. The study used the acid-cleavable dialkoxydiphenylsilane (DADPS) linker to release the probe–peptide

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• Field (AEIF), which are calculated for each CPA substituent (R) by observing the electrostatic potential of a quarternary ammonium ion with the substituent of interest (NMe3R+). The authors performed unsupervised clustering on an in silico library to select a ‘Universal Training Set’ (UTS) consisting of

• implementations were chosen to tackle this problem. In 2022, Denmark and co-workers [132] (Figure 12) investigated a disulfonimide-catalysed atroposelective iodination with the intention of finding a general reaction procedure. After constructing an in silico library consisting of 1,478 catalysts, a universal

Finding the most potent compounds using active learning on molecular pairs

• Zachary Fralish and
• Daniel Reker

Beilstein J. Org. Chem. 2024, 20, 2152–2162, doi:10.3762/bjoc.20.185

• (D-MPNN) Chemprop [20]. For our evaluation with tree-based models, we selected XGBoost [21] with readily available GPU acceleration [26]. Standard, single-molecule machine learning models were implemented using the single-molecule mode of Chemprop [12][27], XGBoost from the XGBoost library [22], and

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• ; flow chemistry; Negishi; on-DNA chemistry; Introduction DNA-encoded chemical library (DEL) technology is a powerful tool for hit identification [1][2]. DELs are chemically synthesized libraries in which every member is covalently attached to a unique DNA sequence serving as a molecular “barcode” [3

• complexity of DELs, there is only limited opportunity to track the efficiency of individual reactions during library synthesis. Therefore, BBs need to pass validation before being used in library synthesis settings. For these bifunctional amino esters, we performed a three-step validation where they were

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• reactions, if we exclude a 96-member library of GBB adducts reported very recently by Dömling et al. [9]. In this case, however, Sc(OTf)3 was used as the catalyst and the choice for ethylene glycol was dictated by the need to have a polar solvent with a high boiling temperature. Shankar et al., however

• . Brunschweiger et al. employed the compartmentation strategy to overcome synthetic problems related to the preparation of a DNA-encoded GBB library [17]. DNA-encoded libraries (DELs) are widely used in screening projects, allowing the synthesis of a huge number of compounds as pools, and the identification of

• cyclophanyl-imidazole-based library of ligands. The synthesis of ligands based on the [2.2]paracyclophane (PCP) moiety, thanks to its structural features and inherent planar chirality upon selective substitution, has been recently reviewed by the same author [46]. Starting from 4-formylcyclophane 37, a GBB

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• , and contain nitrogen, boron, oxygen, and sulfur atoms. Using these building blocks, we generated a chemical library of cata-condensed hetero-PASs (cc-hPASs) ranging in size from 3- to 10-ring systems, by combining the rings according to the annulation types shown in Figure 1B. The number, type, and

• some of the building blocks contained in the COMPAS-2 library can only annulate linearly (specifically, cyclobutadiene, pyrazine, 1,4-diborinine, 1,4-dihydro-1,4-diborinine), this dataset shows a greater density of structures close to the “rod” vertex and along the “rod/disc” edge of the PMI plot

• distribution of the COMPAS-1 molecules (light blue) is contained within the distribution of the COMPAS-2 molecules (purple). In other words, the expansion of the building block library widens the property distributions towards both higher and lower energies, providing access to functional molecules with

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• clinical strains isolated from patients in Mexico: S. epidermidis MIQ43 (multidrug-resistant clinical sample) (internal code from the MicroIQ laboratory library), and P. aeruginosa MIQPA25 [54] (multidrug-resistant clinical sample isolated from cystic fibrosis patients), and C. difficile R20291. All

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• University, Svobody sq., 4, 61022, Kharkiv, Ukraine 10.3762/bjoc.20.156 Abstract By one-pot four- and three-component Ugi reactions involving convertible isocyanides and unexplored pyrrole-containing β-chlorovinylaldehyde, a small library of 20 bisamides with unusual behavior in post-Ugi transformations was

• -4CR reaction and post-transformation of the corresponding bisamide 8c. Plausible transformation sequence of the formation of amides 10 and ketobisamides 12. Library of Ugi bisamides 5–8 containing a β-chlorovinyl fragment. Post-Ugi transformations of bisamides 5–8 under different conditions

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• , such as a one-pot four-component synthesis and the use of ionic liquids as solvents [30]. Kanchithalaivan et al. [31] reported a library of 16-spiro pyrrolo[1,2-c][1,3]thiazoles of trans-androsterone and DHEA (49a and 49b, respectively). The syntheses were achieved through the 1,3-dipolar cycloaddition

• tolylhydrazonoyl chloride derivative 54 [35]. The reaction conducted in the presence of silver acetate at room temperature, achieved yields of 78–81% of the 16-spiropyrazolines 55a,b (Scheme 17). 6-Spiroimidazoline steroids In 2015, Dar’s group reported a small library of spiroimidazo[1,2-a]pyridines obtained

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• -adapted CE was isolated from a fosmid genomic library of Microbulbifer thermotolerans DAU221 with a similar catalytic triad and expressed in E. coli [56]. Other enzymes Chondroitinases (ChSases) are enzymes that digest chondroitin sulfate chains to generate disaccharides. They can be classified into

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• involving the use of Sc(OTf)3 and TsOH as the catalysts were tested on a broad substrate scope, and prevalence of the first method was clearly demonstrated. Furthermore, the scope and limitations of the procedure were established. A model 790-member library was obtained with 85% synthesis success rate

• allowed obtaining the target library member in pure form) on a large set of starting materials. Through the article, the compound numbering system common for the works on combinatorial chemistry was used: the starting materials used for the library generation were marked as 1{i}, 2{j}, and 3{k}, whereas

• the corresponding library members were denoted as 4{i,j,k}. Results and Discussion Library synthesis Preliminary experiments on the parallel GBB reaction were performed with heterocyclic amines 1{1–430}, aldehydes 2{1–583}, and isonitriles 3{1–73} available from our stock (based on our previous in